The present invention is various novel analogs of pyrazolo[4,3-d]pyrimidine-5,7-(4H,6H)-dione and also -5-thione-7-ones, novel methods of synthesis, compositions, and uses thereof. The use relates particularly to the analogs desirable affinity at Al adenosine receptors, advantageous inhibition of phosphodiesterase and desirable central nervous system and cardiovascular activities. For example, the analogs stimulate the central nervous system, reverse bronchoconstriction, and act as cardiac stimulants and cardiotonic agents. The preferred method of use for the novel analogs of the present invention is for the treatment of bronchoconstriction and cardiac insufficiency.
R. K. Robins, et al, J.O.C. 21(8), 833 (1956) report a compound having the Formula X ##STR1## as a potential purine antagonist for chemotherapy but do not suggest the utility of the present invention. The same authors also report the chemical synthesis of a compound of Formula XX ##STR2## wherein Hal is chlorine or bromine by a reaction of the unsubstituted cyclized compound of Formula XXX ##STR3## with dimethylsulfate in JACS, 78, 2418 (1956). The unsubstituted cyclized compound XXX is disclosed as isoxanthine by R. F. Rose in J. Chem. Soc., 3448 (1952). No utility is mentioned for either the compound of Formula XX or of Formula XXX. Further, synthesis for a compound having the Formula XL ##STR4## is given by V. Papesch, et al, in J.O.C. 30, (1) 199 (1965). UV comparisons of 3,4d versus 4,3d ring systems having the appropriate empirical formula appear in Ind. J. Chem. Sec B, 21B, (6), 585-6 (1982).
There is no teaching to the combination and location of the substituents on the 4,3-d ring system of the compounds of the present invention. Further, the compounds of the present invention cannot be made by any methods of the above discussed references.
Many references disclose oxipurinol type compounds which are distinguished by a different ring system, i.e., [3,4-d] ring system. The [3,4-d] ring systems do not teach the present invention having the [4,3-d] ring system. For example, Japanese 77 05.794 discloses 4-hydroxy and 4,6-dihydroxy-1H-pyrazolo[3,4-d]pyrimidine of Formula L ##STR5##